Despite the success of antiretroviral interventions to prevent mother to child transmission of HIV, pediatric HIV infection continue to be a major pubic heath concern. According to the UNAIDS 2010 report, more than 350,000 infants were infected with HIV in 2009. Breastfeeding is responsible for almost half of infant HIV infections. Thus, there is an urgent need to develop a vaccine to prevent postnatal HIV acquisition. As the neonatal immune system presents specific challenges to effective vaccination, it is unclear if results of HIV vaccine studies in adults can predict the outcome of infant vaccination with similar vaccine regimens. The moderate 31 % protection observed in adults from the recently completed canarypox prime-protein boost RV144 trial has brought new hopes for an effective transmission-blocking vaccine to the HIV vaccine research field. In fact, vaccine -elicited nonneutralizing antibody responses against.the V1V2 region of the HIV Envelope (Env) have been associated with the observed protection. This study provides a benchmark by which all previous and future vaccine trials can be compared. The Pediatric AIDS Clinical Trial Group protocol (PACTG) 230 and 326 are two of the main pediatric HIV vaccine trials conducted to date. PACTG 230 assessed two gp120 vaccines in HIV-exposed infants and PACTG 326 evaluated a canarypox-prime, gp120 protein boost strategy similar to that to RV144. The infant vaccines induced HIV-specific antibodies, but the specificity and function of these antibodies have not been characterized. Interestingly, neonatal macaques passively immunized with a broadly neutralizing monoclonal antibody had more potent functional responses following challenge with a Simian-Human immunodeficiency virus than untreated, challenged neonates. This result indicates that maternally-acquired antibodies influence HIV-specific antibody functional responses following vaccination of HIV-exposed infants. We propose to investigate the epitope and class specificity, as well as the neutralizing and non-neutralizing functions of HIV-specific antibodies in HIV- exposed, vaccinated infants from PACTG 230 and 326 infant vaccine trials. The antibody responses in infants will be compared to those in adults who received the moderately-protective RV144 vaccine to determine whether a similar protective response, such as the V1V2-specific IgG response, may have been elicited by these infant vaccine regimens. This study will bring important new insights into the differences in the adult and HIV-exposed infant Env vaccine-elicited responses, information that is critical for the development of infant HIV vaccine strategies based on vaccines that are proven to be protective in adult populations. PUBLIC HEALTH RELEVANCE: With over 300,000 infections every year, pediatric HIV continues to be a major public health issue and there is an urgent need to develop an efficient vaccine. However, because the infant immune system is immature, it is unclear if HIV vaccine strategies developed in adults would be applicable to infant vaccination. The goal of this study is to investigate the fine specificity and function of vaccine-induced HIV-specific antibody responses in HIV-exposed infants, and compare infant responses to those of vaccinated adults from the moderately protective R144 HIV vaccine trial. Determining whether infant HIV vaccination elicited antibody responses similar to that of the moderately protective adult HIV vaccine is the logical next step in infant HIV vaccine design.